The CNS is a sanctuary for leukemic cells in mice receiving imatinib mesylate for Bcr/Abl-induced leukemia

Nicholas C. Wolff, James A. Richardson, Merrill Egorin, Robert L. Ilaria

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Abstract

The chronic myelogenous leukemia (CML)-like myeloproliferative disorder observed in the BCR/ABL murine bone marrow transduction and transplantation model shares several features with the human disease, including a high response rate to the tyrosine kinase inhibitor imatinib mesylate (STI571). To study the impact of chronic imatinib mesylate treatment on the CML-like illness, mice were maintained on therapeutic doses of this drug and serially monitored. Unexpectedly, despite excellent systemic control of the CML-like illness, many of the mice developed progressive neurologic deficits after 2 to 4 months of imatinib mesylate therapy because of central nervous system (CNS) leukemia. Analysis of imatinib mesylate cerebral spinal fluid concentrations revealed levels 155-fold lower than in plasma. Thus, in the mouse, the limited ability of imatinib mesylate to cross the blood-brain barrier allowed the CNS to become a sanctuary for Bcr/Abl-induced leukemia. This model will be a useful tool for the future study of novel anti-CML drugs and in better defining the mechanisms for limited imatinib mesylate penetration into the CNS.

Original languageEnglish (US)
Pages (from-to)5010-5013
Number of pages4
JournalBlood
Volume101
Issue number12
StatePublished - Jun 15 2003

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Neurology
Leukemia
Central Nervous System
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myeloproliferative Disorders
Neurologic Manifestations
Imatinib Mesylate
Blood-Brain Barrier
Bone Marrow Transplantation
Pharmaceutical Preparations
Protein-Tyrosine Kinases
Bone
Therapeutics
Plasmas
Fluids

ASJC Scopus subject areas

  • Hematology

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The CNS is a sanctuary for leukemic cells in mice receiving imatinib mesylate for Bcr/Abl-induced leukemia. / Wolff, Nicholas C.; Richardson, James A.; Egorin, Merrill; Ilaria, Robert L.

In: Blood, Vol. 101, No. 12, 15.06.2003, p. 5010-5013.

Research output: Contribution to journalArticle

Wolff, Nicholas C. ; Richardson, James A. ; Egorin, Merrill ; Ilaria, Robert L. / The CNS is a sanctuary for leukemic cells in mice receiving imatinib mesylate for Bcr/Abl-induced leukemia. In: Blood. 2003 ; Vol. 101, No. 12. pp. 5010-5013.
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